OBJECTIVES: Impaired microvascular perfusion within the brain, demonstrated following periods of cardiac arrest, likely is an important determinant of the diffuse brain injury resulting therefrom. The proposed investigation will examine the possible therapeutic effects of some agents on local cerebral blood flow following circulatory arrest. Cardiac arrest in excess of five minutes duration will be induced by ventricular fibrillation in mongrel dogs and in rhesus monkeys. The cessation of cardiac activity is known to lead to significant deficiencies in cerebral circulation and to zones of no-reflow in the period after resumption of cardiac activity (see Section 2b). The effectiveness of therapy will be assessed by a comparison between untreated animals and those receiving one or more of the following: hyperosmolar preparations, barbiturates ergot alkaloids, heparin. Microvascular perfusion patency will be assessed in the post arrest period by cerebral angiography, and by the colloidal carbon perfusion technique. Regional cerebral blood flow will be measured by the C-14 antipyrine autoradiographic method and Xe 133 injection. The obsevations will be useful in understanding more precisely the changes in cerebral hemodynamics produced by cardiac arrest. A knowledge of the effectiveness of the therapeutic agents examined could potentially be of value in the management of humans with cardiac arrest and related cerebral vascular disorders.